Is BGLAP p.Asp85Gly (c.254A>G) pathogenic?

BGLAP p.Asp85Gly (c.254A>G) is classified Uncertain significance in BGLAP (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-04). AlphaMissense: likely pathogenic (0.7162); Absent from gnomAD v4.1.

How common is BGLAP p.Asp85Gly (c.254A>G) in the general population?

BGLAP p.Asp85Gly (c.254A>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about BGLAP p.Asp85Gly (c.254A>G)?

AlphaMissense predicts likely pathogenic (score 0.7162) — an in-silico prediction, not a clinical call.

BGLAP p.Asp85Gly

c.254A>G · VCV4206749

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.7162 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.7162	likely pathogenic
REVEL	0.63	indeterminate
SaProt	LLR -9.33	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL makes no call.
Splicing
SpliceAI	Δ0.21	acceptor loss, 17 bp away · masked 0 · deltas
Constraint at this position
Conservation	phyloP 11	GERP 0.66, phastCons 1
Regional constraint	o/e 0.89	unconstrained · MANE · 927 bp · p 0.22 · regional, not allelic
Overall
CADD	26.2	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: BGLAP
Protein: p.Asp85Gly
Coding: c.254A>G
MANE Select: NM_199173
Type: single nucleotide variant
Location: chr1:156243113 (GRCh38)
Gene constraint: LOEUF 1.795 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 76.66 · 9 PDB
Residue 85: the gla domain

Full BGLAP gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

BGLAP p.Ala23Val Uncertain significance ★ ⚠ same type
BGLAP p.Arg94Trp Uncertain significance ★ ⚠ same type
BGLAP p.Asp81Glu Uncertain significance ★ ⚠ same type
BGLAP p.Gly27Ser Uncertain significance ★ ⚠ same type
BGLAP p.Gly88Ser Uncertain significance ★ ⚠ same type
BGLAP p.Gly98Ser Uncertain significance ★ ⚠ same type
BGLAP p.Ile87Met Uncertain significance ★ ⚠ same type
BGLAP p.Leu15Phe Uncertain significance ★ ⚠ same type

Built on 18 open, versioned datasets — ClinVar, gnomAD, AlphaMissense, REVEL, ClinGen & more — plus Sugi Variant's own cross-source analysis. Source data 2026-01–2026-10, ClinVar 2026-10. Full sources & versions →

Cite Sugi Variant

Gür T. Sugi Variant: A Deterministic Per-Variant Germline Reference from a Knowledge Graph for Humans and AI Agents. 2026. doi:10.5281/zenodo.21509445. This variant: https://sugi.bio/variant/bglap-p-asp85gly (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown